PROPERTIES OF GABA(A) RECEPTORS UNDERLYING INHIBITORY SYNAPTIC CURRENTS IN NEOCORTICAL PYRAMIDAL NEURONS

Rapid applications of GABA (from 10 mu M to 10 mM) to outside-out patc hes were used to study the role that the kinetic properties of GABA(A) receptors play in determining the time course of IPSCs in neocortical pyramidal neurons. Currents induced by rapid applications of brief (1 msec) pulses of GABA (1 mM) showed a biexponential decay phase that s eems to involve the entry of GABA(A) receptors into desensitized slate s, This conclusion is based on the similar fast decay kinetics of the response to brief and prolonged pulses of GABA and on the correlation between the degree of paired-pulse depression and the decay rate of th e currents induced by brief pulses. Under nonequilibrium conditions we found that the concentration-response curve of pyramidal GABA(A) rece ptors has an EC50 of 185 mu M (GABA pulse of 1 msec). The decay time c ourse of the patch currents in response to brief applications of GABA was insensitive to agonist concentrations at the range from 50 mu M to 10 mM. Faster decay rates were observed only in response to pulses of 10 mu M GABA. These data are compatible with the suggestion that brie fer openings derive from a monoliganded state and that these are negli gible when receptor activation is >2%, Assuming that GABA transients a t neocortical synapses are fast, a several millimolar GABA concentrati on would be needed to saturate the postsynaptic GABA(A) receptors.